Pharmacological effect of Clozapine on emotional disfunction in a rat model of vulnerability to stress

氯氮平对应激大鼠模型情绪障碍的药理作用

• 批准号: 19591376
• 负责人: ISHIGOOKA Jun
• 金额: $ 2.08万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19591376/
• 关键词: 恐怖条件づけ; ドパミン; マイクロダイアリシス; 抗精神病薬; クロザピン; 統合失調症; 扁桃体; 覚せい剤過感受性; 脆弱性; 恐怖条件付け; 脳内微小透析法

Aripiprazole and haloperidol equally suppressed the marked increase in extracellular dopamine levels in fear-conditioned rats, whereas haloperidol increased and aripiprazole decreased basal dopamine levels. The effect of antipsychotics would attenuate the dopamine fear response in the amygdala, modulating basal dopamine level.Both of haloperidol and clozapine significantly increased the basal dopamine level in the basolateral nucleus of amygdala in a dose-related fasion ; the maximum proportionate increase in the clozapine groups was significantly greater than in the haloperidol groups. The extracellular dopamine level in the basolateral amygdala was significantly elevated after conditioned fear stress. Both clozapine and haloperidol suppressed this dopamine fear response. Suppression of fear response of dopamine by clozapine and haloperidol suggests that these antipsychotic agents affect the mechanism of dopamine release, at least in the amygdala.

阿立哌多尔唑和氟哌啶醇在恐惧条件大鼠中同样抑制了细胞外多巴胺水平的明显增加，而氟哌啶醇则增加，而阿ipiprazole降低了基础多巴胺水平。抗精神病药的作用会减弱杏仁核中多巴胺的恐惧反应，调节基础多巴胺水平。氟哌啶醇和氯氮平的均显着提高了与剂量相关的法剂的基底外侧核的基底多巴胺水平；氯氮平基组的最大比例增加明显大于氟哌啶醇基团。条件恐惧应激后，基底外侧杏仁核的细胞外多巴胺水平显着升高。氯氮平和氟哌啶醇都抑制了这种多巴胺的恐惧反应。氯氮平和氟哌啶醇抑制多巴胺对多巴胺的恐惧反应表明，这些抗精神病药会影响多巴胺释放的机理，至少在杏仁核中。

项目成果

Difference in effect of haloperidol and aropiprazole on excessive release of dopamine in the amygdala induced by conditioned fear stress in methamphetamine-sensitized rats.

氟哌啶醇和阿罗哌唑对甲基苯丙胺致敏大鼠条件性恐惧应激引起的杏仁核多巴胺过度释放的影响差异。

• 发表时间: 2008
• 作者: Oshibuchi H;Sugawara H;Inada K;Ishigooka J
• 通讯作者: Ishigooka J

Action of amygdala dopamine and effect of antipsychotics.

杏仁核多巴胺的作用和抗精神病药物的作用。

• 发表时间: 2010
• 期刊: Jpn. J. Neuropsychopharmacol. 30
• 作者: Oshibuchi H;Inada K;Ishigooka J
• 通讯作者: Ishigooka J

The effect of antipsychotic agents to enhancement of release of dopamine in the amygdala induced by conditioned fear stress; in vivo microdialysis study.

抗精神病药物对条件性恐惧应激引起的杏仁核多巴胺释放的增强作用；

• 发表时间: 2009
• 作者: Oshibuchi H;Inada K;Sugawara H;Ishigooka J
• 通讯作者: Ishigooka J

The effect of clozapine to enhancement of release of dopamine in the amygdala induced by conditioned fear stress; in vivo microdialysis study.

氯氮平增强条件性恐惧应激引起的杏仁核多巴胺释放的作用；

• 发表时间: 2008
• 作者: Oshibuchi H;Inada K;Sugawara H;Ishigooka J
• 通讯作者: Ishigooka J

Antipsychotic agents attenuate dopamine fear response in the basolateral amygdala by modulating basal dopamine release; an in vivo microdialysis study.

抗精神病药物通过调节基础多巴胺的释放来减弱基底外侧杏仁核的多巴胺恐惧反应；

• 发表时间: 2009
• 作者: Oshibuchi H;Inada K;Sugawara H;Ishigooka J
• 通讯作者: Ishigooka J